Abstract
The relationship between parasite fitness and virulence has been the object of experimental and theoretical studies often with conflicting conclusions. Here, we provide direct experimental evidence that viral fitness and virulence, both measured in the same biological environment provided by host cells in culture, can be two unrelated traits. A biological clone of foot-and-mouth disease virus acquired high fitness and virulence (cell killing capacity) upon large population passages in cell culture. However, subsequent plaque-to-plaque transfers resulted in profound fitness loss, but only a minimal decrease of virulence. While fitness-decreasing mutations have been mapped throughout the genome, virulence determinants—studied here with mutant and chimeric viruses—were multigenic, but concentrated on some genomic regions. Therefore, we propose a model in which viral virulence is more robust to mutation than viral fitness. As a consequence, depending on the passage regime, viral fitness and virulence can follow different evolutionary trajectories. This lack of correlation is relevant to current models of attenuation and virulence in that virus de-adaptation need not entail a decrease of virulence.
Highlights
The relationship between fitness and virulence is an unsettled question, and sometimes fitness is considered a component of the virulence phenotype of parasites
We describe the behavior of an footand-mouth disease virus (FMDV) clone (H595), which has a history of repeated serial plaque-to-plaque transfers in baby hamster kidney 21 (BHK-21) cells [11], that attained a very low fitness value relative to its parental reference virus (C-S8c1), and yet, its virulence for BHK-21 cells was significantly higher than that of C-S8c1
We use foot-and-mouth disease virus (FMDV) to document that virulence and fitness— measured in the same biological environment provided by cells in culture—can be unrelated traits
Summary
The relationship between fitness and virulence is an unsettled question, and sometimes fitness is considered a component of the virulence phenotype of parasites. RNA viruses are ideal systems to address this important question because of their high mutability and fecundity, which result in a potential for rapid evolution, and because of the availability of quantitative fitness and virulence assays. RNA viruses replicate as complex and dynamic mutant spectra, termed viral quasispecies. Key to quasispecies dynamics are mutation rates in the range of 10À3 to 10À5 substitutions per nucleotide copied, and competition among continuously arising variant genomes [1,2,3,4], which prompt rapid movements in sequence space, with corresponding changes of position in the fitness landscape [5]. Fitness recovery of low fitness footand-mouth disease virus (FMDV) clones occurs mainly with introduction of mutations along the genome, with very few true reversions
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